Summary:

The overall objective is to generate human monoclonal antibodies (HumAbs) with specificity for Plasmodium falciparum antigens of importance in acquired protection to P. falciparum-induced malaria. The specific objectives are: (i) to generate HumAbs with specificity for antigens exposed on the surface of infected erythrocytes, (ii) to generate HumAbs with specificity for variants of the PfMSP1 antigen and (iii) to test the reactivity and specificity of the developed HumAbs with respect to P. falciparum isolates obtained from infected individuals.

An innovative technology developed by a member of the consortium allows for the efficient generation and production of HumAbs. It will be applied in order to generate antibodies with specificity for PfMSP1 and PfEMP1. Both these antigens are strongly implicated in protective immunity to P. falciparum infection, based on recent research data. The project goes clearly beyond the current state-of-the-art in malaria research by combining groundbreaking technology with rational, evidence-based selection of candidate parasite antigens as targets of therapeutic and prophylactic intervention. The approach holds the promise of overcoming existing obstacles to achieve efficient intervention against malaria.

Background:

The main antigenic targets of the protective immunity to P. falciparum infection, as developed by people living in areas of stable parasite transmission, are expressed on the intact surface of infected erythrocytes or free merozoite stage parasites, and are encoded either by polymorphic single-copy genes or by clonally variant multi-gene families. This has greatly obstructed traditional approaches towards the development of effective vaccines as new prophylactic interventions against malaria.

Aim:

To develop panels of human monoclonal IgG antibodies with specificity for a representative polymorphic single-copy antigen (PfMSP1) and for specific members of the PfEMP1 antigens encoded by the clonally variant var multigene family.

Expected results:

“Proof-of-principle” data by developing HumAbs with specificity for a representative polymorphic single-copy antigen (PfMSP1) and for specific members of the PfEMP1 antigens encoded by the clonally variant var multigene family.

Potential applications:

Malaria vaccine research tools and passive therapeutic immunization.

Coordinator:

Partners:

Nº	Principal Scientific Participants	Official Address	Other Information
2	Antonio Lanzavecchia	Institute for Biomedical Research Via Vincenzo Vela 6 6500 Bellinzona Switzerland	Tel.: +41 91 8200310 Fax: +41 91 8200312 E-mail: lanzavecchia@irb.unisi.ch Web-site: www.irb.unisi.ch
3	Anthony Holder	Division of Parasitology The National Institute for Medical Research The Ridgeway Mill Hill London NW7 1AA UK	Tel.: +44 208 959 3666/ 2175 Fax: +44 208 913 8593 E-mail: aholder@nimr.mrc.ac.uk Web-site: www.nimr.mrc.ac.uk
4	John Lusingu	Department of Epidemiology and Clinical Trials National Institute for Medical Research, Tanga Tanzania